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Record W3020250265 · doi:10.21037/tau.2020.04.05

Genetics of CFTR and male infertility

2021· review· en· W3020250265 on OpenAlexaff
Jared M. Bieniek, Craig Lapin, Keith Jarvi

Bibliographic record

VenueTranslational Andrology and Urology · 2021
Typereview
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsMount Sinai HospitalUniversity of Toronto
Fundersnot available
KeywordsCystic fibrosisCystic fibrosis transmembrane conductance regulatorMale infertilityInfertilityBiologyGenetic testingMedicineInternal medicineGeneticsEndocrinologyPregnancy

Abstract

fetched live from OpenAlex

Abstract: Cystic fibrosis (CF) is a rare autosomal-recessive disorder manifested as multisystem organ dysfunction. The cystic fibrosis transmembrane conductance regulator (CFTR) protein functions as an ion transporter on the epithelium of exocrine glands, regulating secretion viscosity. The CFTR gene, encoded on chromosome 7, is required for the production and trafficking of the intact and functional CFTR protein. Literally thousands of human CFTR allelic mutations have been identified, each with varying impact on protein quality and quantity. As a result, individuals harboring CFTR mutations present with a spectrum of symptoms ranging from CF to normal phenotypes. Those with loss of function but without full CF may present with CFTR-related disorders (CFTR-RDs) including male infertility, sinusitis, pancreatitis, atypical asthma and bronchitis. Studies have demonstrated associations between higher rates of CFTR mutations and oligospermia, epididymal obstruction, congenital bilateral absence of the vas deferens (CBAVD), and idiopathic ejaculatory duct obstruction (EDO). Genetic variants are detected in over three-quarters of men with CBAVD, the reproductive abnormality most classically associated with CFTR aberrations. Likewise, nearly all men with clinical CF will have CBAVD. Current guidelines from multiple groups recommend CFTR screening in all men with clinical CF or CBAVD though a consensus on the minimum number of variants for which to test is lacking. CFTR testing is not recommended as routine screening for men with other categories of infertility. While available CFTR panels include 30 to 96 of the most common variants, complete gene sequencing should be considered if there is a high index of suspicion in a high-risk couple (e.g., partner is CFTR mutation carrier). CF treatments to date have largely targeted end-organ complications. Novel CFTR-modulator treatments aim to directly target CFTR protein dysfunction, effectively circumventing downstream complications, and possibly preventing symptoms like vasal atresia at a young age. Future gene therapies may also hold promise in preventing or reversing genetic changes that lead to CF and CFTR-RD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.982
Threshold uncertainty score0.540

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.051
GPT teacher head0.378
Teacher spread0.326 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations53
Published2021
Admission routes1
Has abstractyes

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